Pharmaceutical and cosmetic carrier or composition for topical application

ABSTRACT

A pharmaceutical or cosmetic carrier or composition for topical application characterized by rheological properties which render the carrier or composition semi-solid at rest and a liquid upon application of shear forces thereto. The composition or carrier are prepared by mixing 1-25 percent of a solidifying agent and 75-99 percent of a hydrophobic solvent, by weight, wherein at least one of them has therapeutic or cosmetic benefits, in the presence or absence of a biologically active substance.

This application is a 371 of PCT/IL01/00025 filed Jan. 01, 2001, whichis a continuation-in-part (CIP) of application Ser. No. 09/526,509 filedMar. 16, 2000, now U.S. Pat. No. 6,348,229, and a continuation-in-part(CIP) of application Ser. No. 09/653,267 filed Aug. 31, 2000, whichclaims benefit of provisional Application No. 60/216,162 filed Jul. 03,2000.

FIELD AND BACKGROUND OF THE INVENTION

The present invention relates to a pharmaceutical or cosmetic carrier orcomposition for topical application onto skin and/or mucosal membranes(e.g., the mucosa of the nose, mouth, eye, ear, vagina or rectum). Moreparticularly, the present invention relates to (i) a cosmetic orpharmaceutical carrier or composition characterized by theologicalproperties which render the carrier or composition semi-solid at restand liquid upon application of shear forces (e.g., spread forces)thereto; (ii) methods of preparing same; and (iii) methods of utilizingsame for treating a variety of skin or mucosal membrane diseases ordisorders.

Most of the skin or mucosal membrane diseases or disorders are theresult of inflammation caused by inflammatory agents, such as, but notlimited to, bacterial, fungal, viral, parasitic, autoimmune, allergic,hormonal and/or malignant inflammatory agents. The most common skindiseases or disorders include eczema, psoriasis and dermatitis,including contact dermatitis, atopic dermatitis and seborrheicdermatitis.

Eczema and dermatitis result from inflammatory processes that involvethe upper dermis and epidermis of the skin. When eczema develops, thekeratinocytes in the epidermis distend from one another and fluid isaccumulated there amongst in a process known as spongiosis.

In chronic forms of eczema or dermatitis the main change includethickening of the epidermis, which leads to itching, roughening andscaling of the skin surface. The loss of water from the skin leads toinflammation of the horny layer, which later result in cracked and soreskin.

Dermatitis is further classified into contact dermatitis (allergic ornon allergic), atopic dermatitis and seborrheic dermatitis.

Non allergic contact dermatitis occurs in response to skin irritants,such as acids, alkalis, oils, detergents and solvents.

Allergic contact dermatitis occurs as a result of sensitization torepeated exposure to an antigen. Allergic contact dermatitis appears inskin areas that were in direct contact with the antigen.

Atopic dermatitis, which affects mainly infants, is characterized bysensitization of the skin to a wide range of common antigens.

Seborrheic dermatitis affects the scalp and other hairy areas, the face,and flexural areas and results from yeast or bacteria inducedinflammation. Most people suffer from dandruff which is a mild form ofseborrheic dermatitis.

Psoriasis is a dominant autosomal inherited inflammatory diseasecharacterized by enhanced proliferation of keratinocytes whichproliferation leads to formation of scaly plaques on, for example, theknees, elbows, buttocks, and which are esthetically unpleasant and causediscomfort to the affected subject.

Skin diseases or disorders are usually treated by creams, gels orointments containing antifungal agents, steroidal agents and/orantibacterial agents. In many instances such creams, gels and ointmentsare difficult to spread, result in a greasy and sticky appearance andare usually not appealing for use.

Genital infections are caused by fungal, viral and microbial agents.Genitals infections are treated either systematically, or by the use ofcreams, ointments or pessaries, which usually leak or otherwise fail tospread well and lead to ineffective therapeutic concentration of thetherapeutically active agent(s) therein.

Genital herpes infections are widespread from the 70's and apart fromthe discomfort they inflict, genital herpes infections may, in somecases, develop into severe disease. Presently, there is no effectivemedication for genital herpes.

Trichomoniasis is an infection of the urogenital tract caused due toinfection by the protozoan Trichomonas vaginalis. Trichomoniasis isassociated with uncomfort itching and vaginal excretion in women.

Candidiasis is caused by Candida albicans and results in itching in thegenital area and white discharge therefrom.

Mucosal membrane inflammations can affect other organs such as forexample, the eye. Conjuctivitis, caused by different types of bacteria,such as, but not limited to, Staphylococcus aureus, Streptococcuspneumoniae or Haemophilus influenzae, is generally treated withantibiotic ointments, e.g., bacitracin 500 U/g or gentamicin 0.3 percentophthalmic ointment instilled into the affected eye. The compliance tothese ointments is usually poor due to the sticky feeling they exert

As is evident from the above descriptions, one of the important routesof administration of a drug for treating a skin or mucosal membrane isis by topical application of a drug onto the skin or mucosal membrane.This method is useful for local treatment but it is also possible toapply pessaries via the rectum as an efficient delivery method ofsystemic agents that are not degraded in the intestine.

Many pharmaceutical carriers are presently known, most of them havedisadvantages when topically applied onto the skin or mucosal membranes.For example, when ointments containing petroleum as a carrier areapplied onto a skin wound, metabolic products and excreta from the woundcannot be casily removed therefrom because of the difficulty of passingthrough the hydrophobic petroleum barrier. In addition, the active drugingredient, which is dissolved or dispersed in the petroleum carrier, isnot efficiently absorbed into the wound tissue, thus, the efficacy ofthe drug is affected. Another example is ophthalmologic ointments, whichare applied into the eye, and make the eye area sticky anduncomfortable. Moreover, in physiological aspect, petroleum restrictsrespiration of a wound tissue and is disturbing to the normalrespiration of the skin.

Many groups of drugs including, for example, antibiotic, antifungal,antiinflammatory, anesthetic, analgesic, antiallergic, corticosteroid,retinoid and antiproliferative medications are preferably administeredtypically using a hydrophobic carrier such as petroleum. However, due tothe undesirable consistency of petroleum and similar hydrophobiccarriers, their topical use is limited. An additional disadvantage ofpetroleum-carrier including products relates to the greasy feelingfollowing their topical application to the skin or mucosal membranes.

Besides petroleum, other hydrophobic pharmaceutical carriers are known,including liquid paraffin, lanolin, beeswax, vegetable oil, glycerinmonostearate, higher alcohols, polyethylene glycol and some emulsifyingagents. All of these agents either suffer the limitations describedhereinabove with respect to petroleum or have undesirable (fast) flowproperties.

Several hydrophobic liquids, e.g., mono-and poly-unsaturated oils fromvegetable and marine sources, silicone oils, mineral oils, and liquidhydrophobic plant-derived oils are known for their therapeutic effectswhen applied topically. Oils may also contain essential nutritionalconstituents, such as oil-soluble vitamins (e.g., vitamin A and vitaminE), minerals and other therapeutically effective constituents.Administration of such therapeutic oils in a liquid form does not exertsufficient amounts of the therapeutic agents, because of the oilflow-spread properties. Other examples of therapeutic oils includemineral and silicone oils, which are useful for the treatment of skindehydration and other medical diseases or disorders. These oils are alsoliquid at ambient temperature.

There is thus a widely recognized need for, and it would be highlyadvantageous to have a new pharmaceutical or cosmetic composition orcarrier which is semi-solid at rest and which liquefies upon applicationof shear forces thereto, because such a pharmaceutical or cosmeticcomposition or carrier can be topically applied as a semi-solid onto anaffected area and then turn into a liquid upon spreading, resulting infaster absorption and less greasiness and stickiness.

SUMMARY OF THE INVENTION

According to one aspect of the present invention there is provided apharmaceutical or cosmetic carrier comprising, by weight, 1-25 percentof a solidifying agent and 75-99 percent of a hydrophobic solvent.

According to another aspect of the present invention there is provided amethod of preparing a pharmaceutical or cosmetic carrier, the methodcomprising the steps of mixing a hydrophobic solvent and a solidifyingagent at a temperature above a melting temperature of the solidifyingagent so as to obtain a mixture containing 75-99 percent of thehydrophobic solvent by weight and 1-25 percent of the solidifying agentby weight; and cooling the mixture.

According to yet another aspect of the present invention there isprovided a pharmaceutical or cosmetic composition comprising, by weight,1-25 percent of a solidifying agent and 75-99 percent of a hydrophobicsolvent, wherein at least one of the solidifying agent and thehydrophobic solvent has a therapeutic or cosmetic beneficial effect.

According to still another aspect of the present invention there isprovided a pharmaceutical or cosmetic composition comprising (a) apharmaceutical or cosmetic carrier containing, by weight, 1-25 percentof a solidifying agent and 75-99 percent of a hydrophobic solvent; and(b) a therapeutically or cosmetically effective amount of a biologicallyactive substance.

According to an additional aspect of the present invention there isprovided a method of preparing a pharmaceutical or cosmetic composition,the method comprising the steps of mixing a hydrophobic solvent and asolidifying agent at a temperature above a melting temperature of thesolidifying agent so as to obtain a pharmaceutical or cosmetic mixturecontaining 75-99 percent of the hydrophobic solvent by weight and 1-25percent of the solidifying agent by weight and further mixing into themixture a therapeutically or cosmetically effective amount of abiologically active substance.

According to yet an additional aspect of the present invention there isprovided a method of treating a disease or disorder of a skin or amucosal membrane, the method comprising the step of topicallyadministrating to the skin or the mucosal membrane a pharmaceutical orcosmetic composition containing, by weight, 1-25 percent of asolidifying agent and 75-99 percent of a hydrophobic solvent, wherein atleast one of the solidifying agent and the hydrophobic solvent has atherapeutic or cosmetic beneficial effect

According to a further aspect of the present invention there is provideda method of treating a disease or disorder of a skin or a mucosalmembrane, the method comprising the step of topically administrating tothe skin or the mucosal membrane a pharmaceutical or cosmeticcomposition containing (a) a pharmaceutical or cosmetic carriercontaining, by weight, 1-25 percent of a solidifying agent and 75-99percent of a hydrophobic solvent; and (b) a therapeutically orcosmetically effective amount of a biologically active substance.

According to further features in preferred embodiments of the inventiondescribed below, the solidifying agent is selected from the groupconsisting of at least one long chain fatty alcohol having at least 15carbon atoms in its carbon backbone and at least one fatty acid, havingat least 18 carbon atoms in its carbon backbone.

According to still further features in the described preferredembodiments the solidifying agent includes a substance selected suchthat under ambient conditions, the carrier is semi-solid at rest andliquefies upon application of shear forces thereto.

According to still further features in the described preferredembodiments the hydrophobic solvent is selected from the groupconsisting of at least one marine animal derived oil, at least oneterrestrial animal derived oil, at least one mineral oil, at least onesilicone oil and at least one plant-derived oil.

According to still further features in the described preferredembodiments the hydrophobic solvent includes an oil selected from thegroup consisting of olive oil, soybean oil, canola oil, rapeseed oil,cottonseed oil, coconut oil, palm oil, sesame oil, sunflower oil,safflower oil, rice bran oil, borage seed oil, syzigium aromaticum oil,hempseed oil, herring oil, cod-liver oil, salmon oil, corn oil, flaxseedoil, wheat germ oil, rape seed oil, evening primrose oil, rosehip oil,tea tree oil, melaleuca oil and jojova oil.

According to still further features in the described preferredembodiments the hydrophobic solvent includes an oil selected from thegroup consisting of omega-3 oil and omega-6 oil.

According to still further features in the described preferredembodiments the solidifying agent has at least one alkyl group sidechain in its carbon backbone.

According to still further features in the described preferredembodiments the carbon backbone of the fatty acid and/or the fattyalcohol has at least one hydroxyl group at position α or β.

According to still further features in the described preferredembodiments the carbon backbone of the fatty acid or the fatty alcoholhas at least one hydroxyl group at positions 8-14.

According to still further features in the described preferredembodiments the solidifying agent includes a 12-hydroxy fatty acid.

According to still further features in the described preferredembodiments at least one of the solidifying agent and the hydrophobicsolvent have a therapeutic or cosmetic beneficial effect.

According to still further features in the described preferredembodiments the skin or the mucosal membrane disease or disorderincludes inflammation caused by an inflammatory agent selected from thegroup consisting of a bacterial inflammatory agent, a fungalinflammatory agent, a viral inflammatory agent, a parasitic inflammatoryagent, an autoimmune inflammatory agent, an allergic inflammatory agent,a hormonal inflammatory agent and a malignant inflammatory agent

According to still further features in the described preferredembodiments the skin disease or disorder is selected from the groupconsisting of psoriasis, acne, seborrhea, seborrheic dermatitis,alopecia and excessive hair growth, itching, wounds, burns, cuts,ulcers, seborrheic dermatitis of the face and trunk, seborrheicblepharitis, contact dermatitis, stasis dermatitis and exfoliativedermatitis.

According to still further features in the described preferredembodiments the statics dermatitis is selected from the group consistingof gravitational eczema, varicose eczema and the exfoliative dermatitisis erytyroderma.

According to still further features in the described preferredembodiments the biologically active substance is selected from the groupconsisting of an antibiotic agent, a free radical generating agent, anantifungal agent, an antiviral agent, a non-nucleoside reversetranscriptase inhibitor, a nucleoside-analog reverse transcriptaseinhibitor, a protease inhibitor, a protease inhibitor, a non-steroidalantiinflammatory drug, a steroidal antiinflammatory drug, animmunosuppressant, an antihistamine agent, an antiinflammatory agent, aretinoid agent, a tar agent, an antipruritics agent and a scabicideagent.

According to still further features in the described preferredembodiments (a) the antibiotic agent is selected from the groupconsisting of chloramphenicol, tetracyclines, synthetic andsemi-synthesic penicillins, beta-lactames, quinolones, fluoroquinolnes,macrolide antibiotics, peptide antibiotics, cyclosporines, erytromycinand clinndamycin; (b) the free radical generating agent is benzoylperoxide; (c) the antifungal agent is selected from the group consistingof azoles, diazole, triazole, miconazole, fluconazole, ketoconazole,clotrimazole, itraconazole griseofulvin, ciclopirox, amorolfine,terbinafine, Amphotericin B and potassium iodide; (d) the antiviralagent is selected from the group of flucytosine (5FC), Vidarabine,acyclovir and Gancyclovir; (e) the nucleoside-analog reversetranscriptase inhibitor is selected from the group consisting ofZidovudine, Stavudine and Lamivudine; (f) the non-nucleoside reversetrarscriptase inhibitor is selected from the group consisting ofNevirapine and Delavirdine; (g) the protease inhibitor is selected fromthe group consisting of Saquinavir, Ritonavir, Indinavir, Nelfinavir,Ribavirin Amantadine, Rimantadineand Interferon; (h) theimmunosuppressant is selected from the group consisting of Clobetasolproprionate, Halobetasol proprionate, Betamethasone diproprionate,Betamethasone valerate, Fluocinolone acetonide, Halcinonide,Betamethasone valerate, Fluocinolone acetonide, Hydrocortisone valerate,Triamcinolone acetonide, Hydrocortisone and hexachlorobenzene; (i) theantiinflammatory agent is a vitamin B3 derivative; (j) the retinoidagent is selected from the group consisting of isotretinoin, adapaleneand tretinoin; (k) the tar agent is selected from the group consistingof coal tar and cade oil; (l) the antihistamine agent is doxepinehydrochloride; (m) the antipruritic agent is crotampiton; and (n) thescabicide agent is selected from the group consisting of benzylbenzoate, malathion and crotamiton.

According to still further features in the described preferredembodiments the biologically active substance is effective in thetreatment of psoriasis, acne, seborrhea, seborrheic dermatitis, alopeciaand excessive hair growth, ichthyosis, wounds, burns, cuts, ulcers,psoriasis, seborrheic dermatitis of the face and trunk, seborrheicblepharitis, contact dermatitis, stasis dermatitis or exfoliativedermatitis.

According to still further features in the described preferredembodiments the statics dermatitis is selected from the group consistingof gravitational eczema; varicose eczema, whereas the exfoliativedermatitis is erythroderma.

The present invention successfully addresses the shortcomings of thepresently known configurations by providing a biologically activecarrier or composition, which is semi solid at rest and liquefies uponapplication of shear forces thereto, which is therefore easy to spread,highly absorbable, non greasy and non-sticky and which can be used forto the treatment of a great number of diseases and syndromes affectingthe skin and mucosal membranes.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is herein described, by way of example only, withreference to the accompanying drawing.

FIG. 1 is a photograph demonstrating the therapeutic effects of acorticosteroid composition prepared in accordance with the teachings ofthe present invention administered twice a day for 10 days, to apsoriasis patient. The composition was prepared as described inExample 1. The photograph clearly demonstrates a reduction in thepsoriatic plaques size following the course of treatment.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention is of (i) a pharmaceutical or cosmetic carrier orcomposition for topical application, preferably characterized byrheological properties which render the carrier or composition asemi-solid at rest and a liquid upon application of shear forcesthereto; (ii) methods of preparing same; and (iii) methods of utilizingsame for treating skin or mucosal membrane diseases or disorders.

The principles and operation of the present invention may be betterunderstood with reference to the accompanying descriptions and examples.

Before explaining at least one embodiment of the invention in detail, itis to be understood that the invention is not limited in its applicationto the details of composition set forth in the following description orexamples. The invention is capable of other embodiments or of beingpracticed or carried out in various ways. Also, it is to be understoodthat the phraseology and terminology employed herein is for the purposeof description and should not be regarded as limiting.

According to one aspect of the present invention there is provided apharmaceutical or cosmetic carrier comprising, by weight, 1-25 percentof a solidifying agent and 75-99 percent of a hydrophobic solvent, whichsolvent per se is typically liquid at ambient temperature.

As used herein in the specification and in the claims section thatfollows, the term “carrier” means a base which is, as is defined in theCollins dictionary, the main ingredient of a mixture. Thus, as usedherein a “pharmaceutical carrier” is a pharmaceutical base which is usedin the preparation of pharmaceutical compositions, whereas a “cosmeticcarrier” is a cosmetic base which is used in the preparation of cosmeticcompositions.

According to another aspect of the present invention there is provided amethod of preparing a pharmaceutical or cosmetic carrier. The methodaccording to this aspect of the invention is effected by mixing ahydrophobic solvent and a solidifying agent at a temperature above amelting temperature of the solidifying agent so as to obtain a mixturecontaining 75-99 percent of the hydrophobic solvent by weight and 1-25percent of the solidifying agent by weight; and cooling the mixture,e.g., to room temperature. Preferably, prior to the step of mixing, boththe hydrophobic solvent and the solidifying agent are brought to thetemperature above the melting temperature of the solidifying agent.

According to still another aspect of the present invention there isprovided a pharmaceutical or cosmetic composition comprising, by weight,1-25 percent of a solidifying agent and 75-99 percent of a hydrophobicsolvent, wherein at least one of the solidifying agent and/or thehydrophobic solvent has a therapeutic or cosmetic beneficial effect

According to yet another aspect of the present invention there isprovided a method of preparing a pharmaceutical or cosmetic composition.The method according to this aspect of the invention is effected bymixing a hydrophobic solvent and a solidifying agent at a temperatureabove a melting temperature of the solidifying agent so as to obtain amixture containing 75-99 percent of the hydrophobic solvent by weightand 1-25 percent of the solidifying agent by weight, and cooling themixture, e.g., to room temperature. Preferably, prior to the step ofmixing, both the hydrophobic solvent and the solidifying agent arebrought to the temperature above the melting temperature of thesolidifying agent, e.g., 60-80° C.

Thus, the present invention offers a method of treating a disease ordisorder of a skin or a mucosal membrane, such as, but not limited to, amucosa of a nose, a mucosa of a mouth, a mucosa of an eye, a mucosa ofan ear, a mucosa of a vagina and a mucosa of a rectum. The methodaccording to this aspect of the present invention is effected bytopically administrating to the skin or the mucosal membrane apharmaceutical or cosmetic composition containing, by weight, 1-25percent of a solidifying agent and 75-99 percent of a hydrophobicsolvent, wherein at least one of the solidifying agent and thehydrophobic solvent has a therapeutic or cosmetic beneficial effect.

Most preferably, the amount of the solidifying agent in a pharmaceuticalor cosmetic carrier according to the present invention is about 4percent to about 12 percent, whereas the amount of the hydrophobicsolvent is about 88 percent to about 96 percent of the total weight ofthe carrier. As used herein the term about refers to ±20%.

According to a preferred embodiment of the present invention, thesolidifying agent includes at least one long chain fatty alcohol havingat least 15 carbon atoms in its carbon backbone and/or at least onefatty acid, having at least 18 carbon atoms in its carbon backbone.Preferably, the solidifying agent has at least one alkyl group sidechain in its carbon backbone. Additionally or alternatively, the carbonbackbone of the fatty acid or the fatty alcohol has at least onehydroxyl group at position α and β. Still additionally or alternatively,the carbon backbone of the fatty acid or the fatty alcohol has at leastone hydroxyl group at positions 8-14. According to presently preferredembodiments of the invention, the solidifying agent preferably includesa 12-hydroxy fatty acid.

According to another preferred embodiment of the present invention, thesolidifying agent includes a substance selected such that ambientconditions, the carrier is semi-solid at rest and liquefies uponapplication of shear forces thereto, i.e., has thixotropic properties.

As mentioned above, preferred solidifying agents, according to thepresent invention, include fatty alcohols having 15 or more carbons intheir carbon chain, such as acetyl alcohol and stearyl alcohol (ormixtures thereof). Other examples of fatty alcohols include arachidylalcohol (C20), behenyl alcohol (C22), 1-triacontanol (C30), as well asalcohols with longer carbon chains (e.g., up to C50). The concentrationof the fatty alcohol, required to obtain the thixotropic properties isinversely related to the length of its carbon chains.

Fatty alcohols, derived from beeswax, comprising a mixture of alcohols,where the majority have at least 20 carbon atoms in their carbon chain,are especially suited as solidifying agents according to the presentinvention.

Another preferred class of solidifying agents includes fatty acidshaving 18 or more carbons in their carbon chain, such as and stearicacid, arachidic acid (C20), behenic acid (C22), octacosanoic acid (C28),as well as fatty acids with longer carbon chains (e.g., up to C50), ormixtures thereof.

The concentration of the fatty acid required to obtain a thickenedcarrier is inversely related to the length of its carbon chains. Stearicacid, for example, exerts a considerable thickening effect at about 10percent concentration, whereas behenic acid would obtain the samethickening effect at a 5-percent concentration.

Optionally, the carbon atom chain of the fatty alcohol or the fatty acidmay have at least one double bond.

A further class of solidifying agent according to the present inventioncomprises long chain fatty alcohols or fatty acids, wherein the carbonatom chain is branched. In an additional preferred class of solidifyingagents, the carbon chain of the fatty acid is substituted with ahydroxyl group, e.g., 12 hydroxy stearic acid.

An important property of the fatty alcohols and fatty acids used incontext of the carrier and composition of the present invention isrelated to their therapeutic properties per se. Long chain saturated andmono unsaturated fatty alcohols, e.g., stearyl alcohol, erycyl alcohol,arachidyl alcohol and docosanol have been reported to possess antiviral,antiinfective, antiproliferative and antiinflammatory properties (see,U.S. Pat. No. 4,874,794, which is incorporated herein by reference).Longer chain fatty alcohols, e.g., tetracosanol, hexacosanol,heptacosanol, octacosanol, triacontanol, etc., are also known for theirmetabolism modifying properties and tissue energizing properties. Longchain fatty acids have also been reported to possess antiinfectivecharacteristics. Thus, the pharmaceutical or cosmetic carrier of thepresent invention provides an extra therapeutic or cosmetic benefit incomparison with currently used vehicles, such as petroleum, which areinert and non-active.

According to still another preferred embodiment of the presentinvention, the hydrophobic solvent includes at least one marine animalderived oil, at least one terrestrial animal derived oil, at least onemineral oil, at least one silicone oil and/or at least one plant-derivedoil. Examples include, but are not limited to, olive oil, soybean oil,canola oil, rapeseed oil, cottonseed oil, coconut oil, palm oil, sesameoil, sunflower oil, safflower oil, rice bran oil, borage seed oil,syzigium aromaticum oil, hempseed oil, herring oil, cod-liver oil,salmon oil, corn oil, flaxseed oil, wheat germ oil, rape seed oil,evening primrose oil, rosehip oil, tea tree oil, melaleuca oil and/orjojova oil.

As used herein “tea tree oil” or “melaleuca oil” both refer todistillates of the leaves of the Australian tree, Melaleucaalternifolia. Tea tree oil is assigned the Chemical Abstract number68647-73-4 and is commercially available from a variety of sources. Teatree oil is recognized as having properties as a solvent, antiseptic,antibacterial, antifungal, and pain reliever, as well as other uses.Melaleuca oil has been used in soaps, shampoos, hand creams, toothpastes, and household cleaners, as well as for treatment of warts andoral candidiasis.

A particularly preferred class of oils to be used in context of thepresent invention include poly-unsaturated oils which contains omega-3and omega-6 fatty acids. Thus, in a presently most preferred embodimentof the present invention the carrier contains at least 6 percent omega-3oil and/or omega-6 oil.

The above described pharmaceutical or cosmetic carrier may be used inthe preparation of a pharmaceutical or cosmetic composition comprising(a) a pharmaceutical or cosmetic carrier containing, by weight, 1-25percent of a solidifying agent and 75-99 percent of a hydrophobicsolvent, which is typically liquid at ambient temperature; and (b) atherapeutically or cosmetically effective amount of a biologicallyactive substance. Preferably, at least one of the solidifying agent andthe hydrophobic solvent has a therapeutic or cosmetic beneficial effect.

As used herein in the specification and in the claims section thatfollows the phrase “biologically active substance” refers to an activeingredient which has a therapeutic or cosmetic effect following itsadministration to an organism (human or animal). The therapeutic orcosmetic effect can be curing, minimizing, preventing or ameliorating adisease or disorder, or improving the physical appearance and aesthetics(e.g., skin hydration) or may have any other therapeutic or cosmeticbeneficial effect The biologically active substance may be, for example,a drug, a vitamin or a vaccine. Thus, the biologically active substancesemployed in context of the present invention are generally selected fromthe broad categories of medicaments, agricultural products and cosmeticproducts. The biologically active substance may be a single drug or acombination of drugs that are dissolved or spread in the carrier of thepresent invention. Therefore, they are usually, yet not obligatorily,hydrophobic. The concentration of the substance is selected so as toexert its therapeutic or cosmetic effect.

According to another aspect of the invention there is provided a methodof preparing a pharmaceutical or cosmetic composition The methodaccording to this aspect of the present invention is effected by (a)mixing a hydrophobic solvent and a solidifying agent at a temperatureabove a melting temperature of the solidifying agent so as to obtain apharmaceutical or cosmetic mixture containing 75-99 percent of thehydrophobic solvent by weight, and 1-25 percent of the solidifying agentby weight; and (b) further mixing into the carrier mixture atherapeutically or cosmetically effective amount of a biologicallyactive substance. Preferably, prior to the step of mixing, both thehydrophobic solvent and the solidifying agent are brought to thetemperature above the melting temperature of the solidifying agent,e.g., 60 -80° C.

According to a preferred embodiment of this aspect of the presentinvention the biologically active substance is an antibiotic agent,e.g., chloramphenicol, tetracyclines, synthetic and semi-synthesicpenicillins, beta-lactames, quinolones, fluoroquinolnes, macrolideantibiotics, peptide antibiotics, cyclosporines, erytromycin andclinndamycin; a free radical, e.g., benzoyl peroxide; a generatingagent; an antifungal agent, e.g., azoles, diazoles, triazoles,miconazole, fluconazole, ketoconazole, clotrimazole, itraconazolegriseofulvin, ciclopirox, amorolfine, terbinafine, Amphotericin B andpotassium iodide; an antiviral agent, e.g., flucytosine (5FC),Vidarabine, acyclovir and Gancyclovir; a non-nucleoside reversetranscriptase inhibitor, Nevirapine and Delavirdine; a nucleoside-analogreverse transcriptase inhibitor, a protease inhibitor, e.g., e.g.,Zidovudine, Stavudine and Lamivudine, a protease inhibitor, e.g.,Saquinavir, Ritonavir, Indinavir, Nelfinavir, Ribavirin Amantadine,Rimantadine and Interferon; a non-steroidal antiinflammatory drug, e.g.,Voltarene; a steroidal antiinflammatory drug; an immuno, e.g.,Clobetasol proprionate, Halobetasol proprionate, Betamethasonediproprionate, Betamethasone valerate, Fluocinolone acetonide,Halcinonide, Betamethasone valerate, Fluocinolone acetonide,Hydrocortisone valerate, Triamcinolone acetonide, Hydrocortisone andhexachlorobenzene; an antihistamine, e.g., doxepine hydrochloride; anantiinflammatory agent, e.g., vitamin B3 or a derivative thereof; aretinoid agent, e.g., isotretinoin, adapalene and tretinoin; a taragent, e.g., coal tar and cade oil; an antipruritics agent, e.g.,crotampiton; or a scabicide agent, e.g., benyl benzoate, malathion andcrotamiton.

The biologically active substance is preferably selected effective inthe treatment of a disease or disorder, such as, but not limited to,psoriasis, acne, seborrhea, seborrheic dermatitis, alopecia andexcessive hair growth, ichthyosis, wounds, burns, cuts, ulcers,psoriasis, seborrheic dermatitis of the face and trunk, seborrheicblepharitis, contact dermatitis, stasis dermatitis (e.g., gravitationaleczema, varicose eczema) or exfoliative dermatitis (e.g., erythroderma).

Thus, the present invention offers another method of treating a diseaseor disorder of a skin or a mucosal membrane, such as, but not limitedto, a mucosa of a nose, a mucosa of a mouth, a mucosa of an eye, amucosa of an ear, a mucosa of a vagina and mucosa of a rectum. Themethod is effected by topically administrating thereto a pharmaceuticalor cosmetic composition containing (a) a pharmaceutical or cosmeticcarrier containing, by weight, 1-25 percent of a solidifying agent and75-99 percent of a hydrophobic solvent, which is typically liquid atambient temperature; and (b) a therapeutically or cosmetically effectiveamount of a biologically active substance.

The pH of the composition or carrier of the present invention ispreferably maintained in the range of about pH 5.5-7.0. Acids, bases,and buffers can be used according to methods well known in the art foradjusting the pH of the carrier or composition.

Pharmaceutical compositions manufactured using the carrier according tothe present invention are very easy to use. When applied on theafflicted body surface of humans or animals, they are in a semi-solidstate, allowing free application without spillage. Upon furtherapplication of a mechanical force, e.g., by rubbing the composition ontothe body surface, it freely spreads on the surface and is rapidlyabsorbed. The ease of the application is demonstrated herein in Example3, where it was compared, in a double blind test to a commercialhydrocortisone preparation. The subjects' score regarding their feelingabout the preparation (e.g., the greasiness, stickiness, absorption,penetration, ease of spreading and lack of shiny look) was significantlyhigher than the score for the commercial preparation.

Additional particulars concerning the use of a variety of biologicallyactive substances in context of the present invention, advantages of thepresent invention over prior art designs and a variety of applicationsof the present invention are provided hereinafter.

Treatment of Wounds

The present invention may find special advantages in the treatment ofwounds. Skin wounds which can be treated using the compositions of thepresent invention include burn wounds, sunburn, cuts, abrasions, acuteand chronic wounds and the like. Treatment of burn, ulcers, acute andchronic wounds typically is directed to keeping the wound as clean aspossible and making the patient as comfortable as possible. It has beenrecognized in this respect that keeping the wound moist is advantageousto patient comfort. While maintaining a moist environment will effectsome cooling of the tissue, it would be advantageous to be able todecrease the intradermal temperature of a burn wound, which would helpto alter the progression of the tissue damage due to heat within thetissues.

Accordingly, it would be advantageous to provide a method for improvedtreatment of a burn wound that permits significant lowering of theintradermal temperature of the burn wound such that the extent of theburn wound may be limited. Compositions which have antimicrobial agentscombined with agents that lead to cooling effect, and which are devoidof adherence to the wound offer relief to people who are suffering fromburns or ulcers. The present invention provides a protective moisturebarrier to contribute to the sterility of the dressing and to maintainthe moistness of the dressing. Sterility is enhanced by thebacteriostatic properties of the wound treatment composition, as well asthe shielding action of the barrier's physical presence. An additionalbarrier to bacteria and contamination is the packaging utilized with thepresent invention and which is addressed in more detail below.

The wound treatment composition of the present invention comprises asthe hydrophobic solvent, for example without limitation, tea tree oil,melaleuca oil and other ingredients in a thixotropic gel formulation. Asstated hereinabove, Tea tree oil, or Melaleuca alternifolia, is anatural plant extract. The unique wound treatment composition, inaddition to creating a moist, soothing environment, is also inherentlybacteriostatic. It helps leave the surface of wounds clean and odorfree. The odor of chronic wounds is a major concern of health careworkers and caregivers. The effectiveness of Melaleuca is increased inthe presence of blood and organic material, rather than decreased as isthe case with other bacteriostatic products. Melaleuca oil is a naturaloil which is considered to be safe and effective on all kinds of cutsand abrasions, surgical wounds, diabetic and mouth ulcers and footfungi.

The application of the composition of the present invention onto cuts,wounds, burns and ulcers is beneficial both in the cure of an infectionor in the protection of the skin from infection. In all such cases, thecomposition of the present invention is easy to use, being semi-solidwhen applied and becoming liquid instantly upon rubbing onto the skin.

Suppositories

For treatment of vaginal infections, suppositories provide an effectivemode for administration of a therapeutic agent Although suppositorieshave attained some success, they have some disadvantages. Most of thecurrent commercial vaginal suppositories, either melt or dissolve in thevaginal tract into an oily or aqueous liquid. This resulting liquid inturn tends to leak out or is expelled out of the vaginal cavityresulting either in soiled clothing and/or inferior efficacy.Accordingly, it is an object of the present invention to provide aneffective antifungal suppository formulation, which overcomes the noteddisadvantages associated with the prior art suppositories.

The suppository formulation of the invention is useful in treatingvaginal fungus infections in mammalian species, such as humans, cats,dogs and the like. The suppository formulation will be easily insertedinto the vaginal cavity and will melt at body temperature soon afterinsertion. Upon melting, the suppository turns into a gel/cream likeconsistency, which will adheres to the vaginal membrane therebyproviding prolonged duration of effectiveness.

As mentioned above, a pharmaceutical or cosmetic composition inaccordance with the teachings of the present invention may include abiologically active substance. The following provides some examples.

Antiviral Agents

The carrier or composition of the present invention is beneficial in thetreatment of viral infections. For example, cold sores are caused by theherpes simplex Type 1 virus and are sometimes referred to as facialherpes. Mollusca are small viral growths that appear singly or in groupson the face, trunk, lower abdomen, pelvis, inner thighs or penis.Shingles (herpes zoster), which usually only occurs once in a lifetime,appears as a rash (clusters of blisters with a red base). It is causedby the same virus responsible for chickenpox. Warts are a common, benignskin tumor caused by viral infection. Eye viral infections, such asviral conjunctivitis is highly contagious and spreads by droplet,fornites, and hand-to-eye inoculation.

Viral infections are currently treated with various antiviral agents, asis summarized in Table 1 below:

TABLE 1 Antiviral drugs Chemical Drug Viruses Type VidarabineHerpesviruses Nucleoside analog Acyclovir H. simplex virus Nucleoside(HSV) analog Gancyclovir Cytomegalovirus Nucleoside (CMV) analogNucleoside-analog reverse transcriptase Retroviruses Nucleosideinhibitors (NRTI): AZT (Zidovudine), (HIV) analog ddI (Didanosine), ddC(Zalcitabine), d4T (Stavudine), 3TC (Lamivudine) Non-nucleoside reversetranscriptase Retroviruses Nucleoside inhibitors (NNRTI): Nevirapine,(HIV) analog Delavirdine Protease Inhibitors: Saquinavir, HIV PeptideRitonavir, Indinavir, Nelfinavir analog Ribavirin Broad spectrum:Triazole HCV, HSV, carboxamide measles, mumps, Lassa feverAmantadine/Rimantadine Influenza Tricyclic A strains amine InterferonsHepatitis B and C Protein

It will be appreciated that the intrinsic antiviral effects of thesolidifying agents, e.g., fatty alcohols and acids, provides asynergistic effect that will result in a higher therapeutic response.

Antiparasite Agents

The biologically active substance contained in a composition of thepresent invention in a therapeutically effective amount may be anantiparasite agent, such as, but not limited to, hexachlorobenzene,carbamate, naturally occurring pyrethroids, permethrin, allethrin,malathion, piperonyl butoxide or mixtures of these drugs.

Antimicrobial Agents

Antimicrobial agents, also referred to as germicidal agents, which maybe used in compositions of the present invention include phenols,including cresols and resorcinols. Antibacterial compositions accordingto the present invention may be used to treat infections of the skin. Anexample of a very common skin infection is acne, which involveinfestation of the sebaceous gland with p. acnes, as well asStaphylococus aurus or Pseudomonas. Various antibacterial agents havebeen utilized to treat acne, however, their efficacy is limited due totheir low penetration into the hydrophobic environment of the sebaceousgland. The composition of the present invention, being hydrophobic bynature would facilitate an enhanced rate of penetration. Examples ofuseful antiacne actives include the keratolytics such as salicylic acid(o-hydroxybenzoic acid), derivatives of salicylic acid such as5-octanoyl salicylic acid, and resorcinol; retinoids such as retinoicacid and its derivatives (e.g., cis and trans); sulfur-containing D andL amino acids and their derivatives and salts, particularly theirN-acetyl derivatives, a preferred example of which is N-acetyl-Lcysteine; lipoic acid; antibiotics and antimicrobials such as benzoylperoxide, octopirox, tetracycline, 2,4,4′-trichloro-2′-hydroxy diphenylether, 3,4,4′-trichlorobanilide, azelaic acid and its derivatives,phenoxyethanol, phenoxypropanol, phenoxyisopropanol, ethyl acetate,clindamycin and meclocycline; sebostats such as flavonoids; and bilesalts such as scymnol sulfate and its derivatives, deoxycholate andcholate.

The intrinsic antibacterial and antiinflammatory effects of thesolidifying agents, i.e., fatty alcohols and acids, of the compositionof the present invention provide a combined synergetic effect thatresults in a better therapeutic response to treatment.

Eye infections are another preferred target for the composition of thepresent invention. Conjuctivitis, involving bacteria such asStaphylococcus aureus, Streptococcus pneumonicae, and Haemophilusinfluenzae is generally treated with antibiotic ointments, e.g.,bacitracin 500 U/g or 0.3 percent ophthalmic ointment instilled into theaffected eye. Yet, ointment applied into the eye created a stickyfeeling and causes major disturbances to the patient. The composition ofthe present invention, which turns from semi-solid consistency intoliquid instantly after application, does not have that disadvantage andthus, treatment compliance is expected to improve. The same advantage isexpected when the composition of the present invention is topicallyapplied to mucosal membranes, the oral cavity, the vagina or the rectum.

Another example is parachlorometaxylenol, which is an antimicrobialagent and is suitable for use in the compositions described in thepresent invention.

Phenols, in concentrations of about 02, 1.0, and 1.3 percent by weightare bacteriostatic, bactericidal, and fungicidal, respectively. While itis not intended that the present invention be bound by any particulartheory, it is believed that the germicidal action of phenols at theseconcentrations is effected through protein denaturation. Thephenol-protein interaction is relatively weak, allowing the phenolmolecule to penetrate deeply into the tissue. Thus, phenol can penetraterelatively dense, intact keratinous matrices, such as the stratumcorneum or the nail plate. Several phenol derivatives are more potentthan phenol itself, and the most important among these are thehalogenated phenols and bis-phenols, the alkyl-substituted phenols andthe resorcinols.

Optionally, the present invention may provide a solution for body odorsby including hydrophobic antibacterial compounds to help destroy and/orcontrol the amount of bacteria present on the skin, which aids in bodyodor control.

Hydrophobic antibacterials useful in the present invention includetriclosan, triclocarbon, eucalyptol, menthol, methylsalicylate, thymol,and mixtures thereof. Preferred are triclosan and triclocarbon. Whenincluded in the composition of the present invention, the hydrophobicantibacterials may be at a level of from about 0.1 percent to about 1.5percent and preferably from about 0.1 percent to about 0.3 percent, byweight of the composition.

Antifungal Agents

Fungal infections are another object of treatment using the compositionsof the present invention. Superficial fungal infection of the skin isone of the commonest skin disease seen in general practice.Dermatophytosis is probably the most common superficial fungal infectionof the skin. It is caused by a group of fungi, which are capable ofmetabolizing the keratin of human epidermis, nails or hair. There are 3genera of dermatophytes causing dermatophytosis i.e., microsporum,trichophyton and epidermophyton.

Candidiasis is an infection caused by the yeast like fungus Candidaalbicans or occasionally other species of Candida. Clinical syndromes ofcandidiasis include (a) oral candidiasis (oral thrush); (b) candidiasisof the skin and genital mucous membrane; and (c) candida paronychia,which inflicts the nail.

The pharmaceutical composition of the present invention can contain anantifungal drug, which is active against dermatophytes and candida. Thedrug may include azoles, diazoles, triazoles, miconazole, fluconazole,ketoconazole, clotrimazole, itraconazole griseofulvin, ciclopirox,amorolfine, terbinafine, Amphotericin B, potassium iodide, flucytosine(5FC) and any combination thereof at a therapeutically effectiveconcentration U.S. Pat. No. 4,352,808 discloses3-aralkyloxy-2,3dihydro-2-(1H-imidazolylmethyl)benzo[b]thiophenecompounds having antifungal and antibacterial activity.

Steroidal Antiinflammatory Agents

Suitable steroidal antiinflammatory agents usable in the composition ofthe present invention may include, although are not limited to,corticosteroids such as hydrocortisone, hydroxyltriamcinolonealphamethyl dexamethasone, dexamethasone-phosphate, beclomethasonedipropionate, clobetasol valerate, desonide, desoxymethasone,desoxycorticosterone acetate, dexamethasone, dichlorisone, diflorasonediacetate, diflucortolone valerate, fluadrenolone, fluclaroloneacetonide, fludrocortisone, flumethasone pivalate, fluosinoloneacetonide, fluocinonide, flucortine butylester, fluocortolone,fluprednidene (fluprednylidene)acetate, flurandrenolone, halcinonide,hydrocortisone acetate, hydrocortisone butyrate, methylprednisolone,triamcinolone acetonide, cortisone, cortodoxone, flucetonide,fludrocortisone, difluorosone diacetate, fluradrenalone acetonide,medrysone, amc, amcinafide, betamethasone and the balance of its esters,chlorprednisone, chlorprednisone acetate, clocortelone, clescinolone,dichlorisone, difluprednate, flucloronide, flunisolide, fluoromethalone,fluperolone, fluprednisolone, hydrocortisone valerate,hydrcyclopentylproprionate, hydrocortamate, meprednisone, paramethasone,prednisolone, prednisone, beclomethasone dipropionate, betamethasonedipropionate, triamcinolone, and mixtures thereof may be used. Thepreferred steroidal antiinflammatory for use in the present invention ishydrocortisone.

Table 2 below provides a summary of currently available corticosteroidagent.

TABLE 2 List of steroidal antiinflammatory agents for topicalapplication Potency Compound Formulation Very high Clobetasolproprionate Cream or ointment 0.05 percent Halobetasol proprionate Creamor ointment 0.05 percent High Betamethasone diproprionate Cream orointment 0.05 percent Betamethasone valerate Ointment 0.1 percentFluocinolone acetonide Cream 0.02 percent Halcinonide Cream or ointment0.1 percent Medium Betamethasone valerate Cream 0.1 percent Fluocinoloneacetonide Cream or ointment 0.020 percent Hydrocortisone valerate Creamor ointment 0.2 percent Triamcinolone acetonide Cream, ointment, orlotion 0.1 percent or 0.020 percent Low Hydrocortisone Cream, ointment,or lotion 2.5 percent or 1.0 percent

Since all corticosteroid drugs are hydrophobic, the carrier of thepresent invention is most suitable as a vehicle to facilitate anenhanced rate of penetration and better topical distribution thereof.

Furthermore, the intrinsic antiviral, antibacterial and antiinflammatoryeffects of the solidifying agents, i.e., fatty alcohols and acids,provide a combined synergetic effect that should result in a bettertherapeutic response to treatment

Psoriasis is a very common chronic inflammatory skin disease, which maybe the target of treatment using a composition of the present invention.Psoriasis is marked by periodic flare-ups of sharply defined red patchescovered by a silvery, flaky surface.

Corticosteroid ointments, greasy preparations containing small amount ofwater, are commonly used for treating psoriasis. Their main disadvantageis in their stickiness, which remains for long time after treatment isover. In this respect it should be noted that the present inventionexemplifies the use of a hydrocortisone containing composition that wasprepared according to the teachings of the present invention (seeExample 1 below). The hydrocortisone preparation was compared to acommercial composition (Example 2) and was shown be highly efficient inthe treatment of psoriatic patients. Major reduction in the severity ofthe disease symptoms, i.e., disappearance of the silvery scales, andreduction of the oedema, erythema and pruritus were observed. Moreoverthe patients reported that unlike the ointments which are currentlyavailable in the market (see Table 2 above), the composition of thepresent invention was well distributed and absorbed into the skin,without leaving an undesirable greasiness and shiny appearance whichcharacterized the prior art formulations.

Examples of other inflammatory diseases or disorders, which can betreated by the composition of the present invention, wherein the drug isa steroid are: seborrheic dermatitis of the face and trunk, seborrheicblepharitis, contact dermatitis, stasis dermatitis (gravitationaleczema; varicose eczema), exfoliative dermatitis (erythroderma), lichensimplex chronicus, pemphigus, conjuctivitis and uveitis.

Topical antihistaminic preparations currently available include 1percent and 2 percent diphenhydramine (Benadryl® and Caladryl®), 5percent doxepin (Zonalon®) cream, phrilamine maleate, chlorpheniramineand tripelennamine, phenothiazines, promethazine hydrochloride(penergan®) and dimethindene maleate. These drugs, as well as additionalantihistamines can also be included in the composition of the presentinvention.

Additionally, so-called “natural” antiinflammatory agents are useful incontext of the present invention. For example, candelilla wax, alphabisabolol, aloe vera, Manjistha (extracted from plants in the genusRubia, particularly Rubia cordifolia), and Guggal (extracted from plantsin the genus Commiphora, particularly Commiphora mukul, may be used asan active ingredient in the composition of the present invention.

Non-steroidal Antiinflammatory Drugs (NSAIDs)

Another preferred embodiment of the present invention is administrationof non-steroidal antiinflammatory drugs (herein NSAIDs) using acomposition of the present invention. NSAIDs have been used extensivelyin recent years for treatment of chronic rheumatic or arthriticconditions and for management of pain. The compounds are believed tobring relief by inhibiting biosynthesis of prostaglandins at affectedjoints or in other tissue areas. Salicylic acid, or aspirin, andibuprofen are well-known examples of NSAIDs drugs. Patients using NSAIDsdrugs administered orally face an increased risk for peptic ulcers andgastrointestinal blood loss resulting in anemia. Such adverse reactionsespecially plague patients taking NSAIDs drugs over prolonged periods.Administration of NSAIDs to using the carrier of the present inventionwill prevent gastrointestinal complications associated with the oraladministration of NSAIDs. Such compositions can be used for prolongedtreatment of arthritis and other diseases or disorders treated by NSAIDsdrugs, while avoiding the gastrointestinal complications associated withoral dose delivery. Application of NSADs drugs in a topical compositionto the skin of a patient allows a predetermined amount of the NSAIDsdrug to be administered continuously to the patient and avoidsundesirable effects present with a single or multiple administrations oflarger dosages. By maintaining a sustained dosage rate, the NSAIDs druglevel in the patient's blood can be better maintained within the optimaltherapeutic range

Examples of NSAIDs include the following categories: propionic acidderivatives; acetic acid derivatives; fenamic acid derivatives;biphenylcarboxylic acid derivatives; and oxicams. All of these NSAIDsare fully described in the U.S. Pat. No. 4,985,459 to Sunshine et al.which is incorporated herein by reference. Examples of useful NSAIDsinclude acetyl salicylic acid, ibuprofen, naproxen, benoxaprofen,flurbiprofen, fenoprofen, fenbufen, ketoprofen, indoprofen, pirprofen,carprofen, oxaprozin, pranoprofen, mniroprofen, tioxaprofen, suprofen,alminoprofen, tiaprofenic acid, fluprofen and bucloxic acid.

Antioxidants/radical Scavengers

Suitable antioxidants/radical scavengers useful in context of thepresent invention include ascorbic acid (vitamin C) and its salts,tocopherol (vitamin E), and its derivatives such as tocopherol sorbate,other esters of tocopherol, butylated hydroxy benzoic acids and theirsalts, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid(commercially available under the trade name Trolox®), gallic acid andits alkyl esters, especially propyl gallate, uric acid and its salts andalkyl esters, sorbic acid and its salts, the ascorbyl esters of fattyacids, amines (e.g., N,N-diethylhydroxylamine, amino-guanidine),sulfhydryl compounds (e.g., glutathione), and dihydroxy fumaric acid andits salts may be used, as well as EDTA, BHT and the like.

Antibiotics

Antibiotics which may be used in context of the composition of thepresent invention, include, but are not limited to, chloramphenicol,tetracyclines, synthetic and semi-synthesic penicillins, beta-lactames,quinolones, fluoroquinolnes, macrolide antibiotics, peptide antibiotics,cyclosporines, erytromycin and clinnidamycin.

Topical Anesthetics

Examples of topical anesthetic drugs useful in context of thecomposition of the present invention include benzocaine, lidocaine,bupivacaine, chlorprocaine, dibucaine, etidocaine, mepivacaine,tetracaine, dyclonine, hexylcaine, procaine, cocaine, ketamine,pramoxine, phenol, and pharmaceutically acceptable salts thereof.

Retinoids

Another preferred group of drugs useful in context of the composition ofthe present invention include retinol, all trans retinoic acid andderivatives, isomers and analogs thereof collectively termed“retinoids”. Compositions according to the present inventio, whichcontain retinoids as the active ingredient can be used for the treatmentof acne, seborrea, various dermatoses, inflammation of the skin, mucosalmembranes, eye, vagina and the rectum, psoriasis and cancers, byapplication onto the affected area

Other Drugs

As is further detailed hereinunder, it is possible to provide thecomposition of the present invention onto a dermal patch to generate atransdermal delivery apparatus and applying such patch onto the skin inorder to attain effective superficial treatment or enhanced penetrationof a drug into the skin or through the skin.

Utilizing such a strategy, one can apply drugs which are currentlyadministered systemically or that require transdermal delivery, in thepreferred therapeutic system of the present invention. The followingprovides some examples for such drugs.

A broad range of analgesics may be utilized including, withoutlimitation, morphine, codeine, heroine, methadone, thebaine, orpiarine,buprenorphine, morphinans, benzomorphans, acetaminophen, butorphanol,diflunisal, fenoprofen, fentanyl, fentanyl citrate, hydrocodone,aspirin, sodium salicylate, ibuprofen, oxymorphone, pentaxicine,naproxen, nalbuphine, mefenamic acid, meperidine and dihydroergotamine.

A typical narcotic antagonist is haloxone. Exemplary antitussive agentsinclude, without timitation, diphenhydramine, guaifenesin,hydromorphone, ephedrine, phenylpropanolamine, theophylline, codeine,noscapine, levopropoxyphene, carbetapentane, chlorpehndianol andbenzonatate.

Among the sedatives which may be utilized are, without limitation,chloral hydrate, butabarbital, alprazolam, amobarbital,chlordiazepoxide, diazepam, mephobarbital, secobarbital,diphenhydramine, ethinamnate, flurazepam, halazepam, haloperidol,prochlorprazine, oxazepam, and talbutal.

Examples of cardiac drugs are, without limitation, quinidine,propranolol, nifedipine, procaine, dobutamine, digitoxin, phenytoin,sodium nitroprusside, nitroglycerin, verapamil HCl, digoxin, nicardipineHCl, and isosorbide dinitrate.

Antiemetics are illustrated by, without limitation, thiethylperazine,metoclopramide, cyclizine, meclizine, prochlorperazine, doxylaminesuccinate, promethazine, triflupromazine, and hydroxyzine.

A typical dopamine receptor agonist is bromocriptine mesylate. Exemplaryamino acid, peptide and protein hormones include, without limitation,thyroxine, growth hormone (GH), interstitial cell stimulating hormone(ICSH), follicle-stimulating hormone (FSH), thyrotropic hormone (TSH),adrenocorticotropic hormone (ACTH), gonadotropin releasing hormone(GnRH) such as leuprolide acetate, vasopressin and their activedegradation products Some products may have sufficiently high molecularweights that absorption through the stratum corneum or mucous membranesmay be difficult. Therefore, the invention is applicable only to thosehormones which have molecular weights and stereo configurations whichwill allow passage through the skin.

Female sex hormones which can be used include, without limitations,estradiol, diethylstilbestrol, conjugated estrogens, estrone,norethindrone, medroxyprogesterone, progesterone, and norgestrel.

Typical male sex hormones which may be utilized may be represented by,without limitation, testosterone, methyltestosterone, andfluoxymesterone.

The above listed active permeants may, along with others notspecifically disclosed, be used separately or in combination accordingto the treatment regimen desired.

Cosmetic Agents

The carrier according to the present invention can also be used toprepare cosmetics for beauty purpose by the addition of skin care agentsand perfumes.

Sun Screen Agents

Also useful in context of the composition of the present invention aresun screening agents. A wide variety of sun screening agents aredescribed in U.S. Pat No. 5,087,445, to Haffey et al. U.S. Pat No.5,073,372, to Turner et al., U.S. Pat. No. 5,073,371, to Turner et al.and Segarin, et al., at Chapter VIII, pages 189 et seq., of CosmeticsScience and Technology all of which are incorporated herein by referencein their entirety. Preferred among those sunscreens which are useful inthe composition of the instant invention are those selected from thegroup consisting of 2-ethylhexyl p-methoxycinnamate, octylmethoxycinnamate, 1-p-aminobenzoate, p-aminobenzoic acid,2-phenylbenzimidazole-5-sulfonic acid, octocrylene, oxybenzone,homomenthyl salicylate, octyl salicylate,4,4′-methoxy-t-butyldibenzoylmethane, 4-isopropyl dibenzoylmethane,3-benzylidene camphor, 3-(4-methylbenzylidene) camphor, titaniumdioxide, zinc oxide, silica, iron oxide, and mixtures thereof. Stillother useful sunscreens are those disclosed in U.S. Pat. Nos. 4,937,370,to Sabatelli and 4,999,186, to Sabatelli et al. These two later isreferences are incorporated by reference herein in their entirety. Thesun screening agents disclosed therein have, in a single molecule, twodistinct chromophore moieties which exhibit different ultra-violetradiation absorption spectra. One of the chromophore moieties absorbspredominantly in the UVB radiation range and the other absorbs stronglyin the UVA radiation range. These sun screening agents provide higherefficacy, broader UV absorption, lower skin penetration and longerlasting efficacy relative to conventional sunscreens. Especiallypreferred examples of these sunscreens include those selected from thegroup consisting of 4N,N-(2-ethylhexyl)methylanminobenzoic acid ester of2,4-hydroxybenzophenone, 4-N,N-(2ethylhexyl)methylaminobenzoic acidester with 4-hydroxydibenzoylmethane,4N,N-(2-ethylhexyl)methylaminobenzoic acid ester of2-hydroxy4-(2-hydroxyethoxy)benzophenone,4-N,N-(2-ethythexyl)-methylaminobenzoic acid ester of4-(2-hydroxyethoxy)dibenzoylmethane, and mixtures thereof. Generally,the sunscreens can comprise from about 0.5 percent to about 20 percentof the compositions useful herein. Exact amounts will vary dependingupon the sunscreen chosen and the desired Sun Protection Factor (SPF).SPF is a commonly used measure of photoprotection of a sunscreen againsterythema. See Federal Register, Vol. 43, No. 166, pp. 38206-38269, Aug.25, 1978.

Artificial Tanning Agents and Accelerators

Examples of artificial tanning agents accelerators which can be used incontext of the present invention include dihydroxyacetone, tyrosine,tyrosine esters such as ethyl tyrosinate, and phospbo-DOPA.

Reducing Body Odors

The body fluids include eccrine sweat, apocrine sweat, sebum, build upof sensible moisture from transepidermal water loss, vaginal discharge,urine, and mixtures thereof. The body odor are odors, which aregenerated as a result of the natural functioning of a human body. Suchodors is include, but are not limited to odors produced bymicroorganisms of the human skin (i.e. bacterial decomposition of skinsecretions), urine, or vaginal discharge, and mixtures thereof. Thepresent invention is therefore relevant to a method of reducing bodyodor comprising the application of a perfume-free, odor-absorbingcomposition, which includes the carrier of the present invention.

Antiwrinkle and Antiskin Atrophy Agents

Examples of antiwrinkle and antiskin atrophy actives which can be usedin context of the present invention include retinoic acid and itsderivatives (e.g., cis and tans); salicylic acid and derivativesthereof, sulfur-containing D and L amino acids and their derivatives andsalts, particularly the N-acetyl derivatives, a preferred example ofwhich is N-acetyl L-gsteine; thiols, e.g. ethane thiol; alpha-hydroxyacids, e.g. glycolic acid, and lactic acid; phytic acid, lipoic acid;lysophosphatidic acid, and skin peel agents (e.g., phenol and the like).

Excipients and Additional Agents

The pharmaceutical or cosmetic composition of the present invention mayfurther include a variety of pharmaceutical or cosmetic ingredients,which are added in order to fine-tune the consistency of theformulation, protect the formulation components from degradation andoxidation and bestow their cosmetic acceptability. Such excipients, maybe selected from the group consisting of water, surfactants,emulsifiers, diglycerides, triglycerides, stabilizing agents,antioxidants, glycerol, ethanol, propanol, isopropanol, butanol,polymeric geuling agents, flavoring, colorant and odorant agents andother formulation components, used in the art of pharmaceutical andcosmetic formulary.

Additional active and inactive ingredients may also include, withoutlimitation, local analgesics such as benzocaine, menthol, and the like(wherein menthol is also capable of providing a soothing, coolingsensation), as well emollients, antihistamines, fragrances, thickenersand preservatives other than those already listed.

Emollients

The compositions of the present invention can also include an emollient.Emollient is used to smooth the surface of the skin. Examples ofsuitable emollients include, but are not limited to, volatile andnon-volatile silicone oils (e.g., dimethicone, cyclomethicone,dimethiconol, and the like), highly branched hydrocarbons, and mixturesthereof. Emollients useful in the instant invention are furtherdescribed in U.S. Pat. No. 4,919,934, to Deckner et al., which isincorporated herein by reference in its entirety. The emollients cantypically comprise in total from about 0.1 percent to about 25 percent,more preferably from about 0.5 percent to about 10 percent, and mostpreferably from about 0.5 percent to about 5 percent by weight of thecomposition.

A variety of additional ingredients can be incorporated into thecomposition of the present invention. Non-limiting examples of theseadditional ingredients include vitamins and derivatives thereof (e.g.tocopherol, panthenol, and the like); other thickening agents (e.g.,polyacrylamide and C₁₃-C₁₄ isoparaffin and laureth-7, available asSepigel 305 from Seppic Corp., Fairfield, N.J.; and branchedpolysaccbarides such as scleroglucan available under the tradenameClearogel® CS 11 from Michel Mercier Products Inc., Mountainside, N.J.);saturated and/or unsaturated alkyl alpha hydroxy acids; resins; gums(e.g. guar gum, xanthan gum and the like); waxes (both naturallyoccurring and synthetic); polymers for aiding the film-formingproperties and substantivity of the composition (such as a copolymer ofeicosene and vinyl pyrrolidone, an example of which is available fromGAF Chemical Corporation as Ganex V-220®); abrasive scrub particles forcleansing and exfoliating the skin, e.g., ACuscrub® Mild Abrasives(e.g., ACuscrub® 30, 31, 32, 40, 41, 42, 43, 44, 50, 51, and 52)available from Allied Signal, Inc., Morristown, N.J.; and 3M Brand PMUCapsules microecapsulated mineral oil available from 3M Corporation, StPaul, Minn.!; preservatives for maintaining the antimicrobial integrityof the compositions; skin penetration aids such as DMSO,1-dodecylazacycloheptan-2-one (available as Azone® from the Upjohn Co.)and the like; skin bleaching (or lightening) agents including but notlimited to hydroquinone, kojic acid and sodium metabisulfite; chelatorsand sequestrants; and aesthetic components such as fragrances, pigments,colorings, essential oils, skin sensates, astringents, skin soothingagents, skin healing agents and the like, nonlimiting examples of theseaesthetic components include panthenol and derivatives (e.g. ethylpanthenol), aloe vera, pantothenic acid and its derivatives, clove oil,menthol, camphor, eucalyptus oil, eugenol, menthyl lactate, witch hazeldistillate, allantoin, bisabalol, dipotassium glycyrrhizinate and thelike.

The carrier system may also comprise, when desired, a suitable gellingagent including, but not limited to, cellulose esters such ashydroxypropyl cellulose (Klucel®), hydroxyethyl cellulose (Natrosol®),polyvinylpyrrolidone (Povidone®), carboxyvinyl polymer (HIVIS 105®) andthe like that may be provided in any amount necessary to thicken thecomposition to a desired gel consistency. When formulated as a gel, thebase composition exhibits favorable spreadability characteristics. Inaddition, it remains visible on the skin surface longer, therebyinstilling in the user the impression that the vehicle is morecompletely delivering its active ingredient(s).

In addition to the aforementioned ingredients, it should also be notedthat the following ingredients may also be included in the inventivecomposition, as desired: coloring agents, fragrances, conditioners,moisturizers, surfactants, antioxidants, preservatives, etc.

Preferred ingredients are saturated and/or unsaturated alkyl alphahydroxy acids, at a level of from about 0.05 percent to about 5 percentby weight of the composition, such as lactic acid, lactate salts (e.g.,ammonium and quaternary alyl ammonium), glycolic acid, glycolate salts(e.g., ammonium and quaternary allyl ammonium), and fruit acids. Adiscussion of alpha hydroxy acids is disclosed in Walter P. Smith,Hydroxy Acids and Skin Aging, Soap/Cosmetics/Chemical Specialties. pp.54-59, (September 1993), which is herein incorporated by reference inits entirety.

Preservatives

Antimicrobial preservatives useful in the present invention includebiocidal and biostatic compounds (substances that kill microorganismsand/or regulate the growth of microorganisms). Suitable antimicrobialpreservatives have a solubility of 0.3 percent or greater. In addition,suitable preservatives are those which can come into contact with skinwithout high irritation potential. Preservatives suitable for use in thepresent compositions are described in U.S. Pat. No. 5,534,165, toPilosof et al.

It is preferable to use a broad spectrum preservative such as one thatis effective both on bacteria (both gram positive and gram negative) andfungi. A limited spectrum preservative such as one that is onlyeffective on a single group of microorganisms, for example fungi, can beused in combination with a broad spectrum preservative or other limitedspectrum preservatives with complimentary and/or supplementary activity.A mixture of broad spectrum preservatives can also be used.

Colorants and Dyes

Colorants and dyes can be optionally added to the odor absorbingcompositions for visual appeal and performance impression. Whencolorants are used, care must be taken in the selection of choosing dyesthat will not color skin. Preferred colorants for use in the presentcompositions are highly water-soluble dyes, e.g., acid blue 3, acid blue104, acid green 1, acid green 25, acid yellow 3, acid yellow 73 sodiumsalt, D&C green No. 5, 6 & 8, D&C yellow No. 7, 8, 10 & 11, D&C violetNo. 2, FD&C blue No. 1 & 2, FD&C green No. 3, FD&C yellow No. 5 & 6, andmixtures thereof.

Other Optional Ingredients

The composition of the present invention can optionally contain adjunctodor-controlling materials, such as zinc salts, cationic polymers,anionic polymers, carbonate salts, bicarbonate salts, zeolites, andactivated carbon; chelating agents; colorants; and/or antiperspirants.

Optionally, the composition of the present invention can include zincsalts for added odor absorption and/or antimicrobial benefit for thecyclodextrin solution. Zinc compounds have been used most often fortheir ability to ameliorate malodor, e.g., in mouth wash products, asdisclosed in U.S. Pat. No. 4,325,939 and U.S. Pat. No. 4,469,674 toShah, et al. Highly-ionized zinc salts, such as zinc chloride, providethe best source of zinc ions. The zinc salt, zinc phenolsulfonate, ispreferred for use in the skin composition of the present invention;although others may also fall within the scope of the present invention.However, care must be taken in selecting zinc salts, as well as theirlevels, since some may be irritants to the skin and they are notpreferred for use in the present invention.

Massage Oils

The compositions of the present invention are particularly suitable toserve as ingredients in massage oils. Unlike conventional massage oils,which are liquid and readily spill upon application, the compositions ofthe present invention are semi-solid when applied and thus, can besafely poured onto the skin without spillage. Once it is rubbed into theskin, the thick texture is brand the oil can be easily massaged. Baseoils of massage formulations often comprise sunflower (Helianthusannuus) oil, canola (Brassica napus/campestris) oil, sweet almond(Prunus amygdalus dulcis) oil, sesame (Sesamum indicum) oil, macadamia(Macadamia ternifolia) nut oil and/or tocopherol (vitamin E).

Essential oils are often added to massage oils. Such essential oilsinclude, for example, oils of mandarin, (Citrus reticulata var.mandarin), sage (Salvia officinalis), geranium rose (Pela graveolensxasperium), palmarosa (Cynbopogon martini), nutmeg (Myristicafrangrans), rosewood (Aniba roseaodora), cedarwood (Juniperusvirginiana), patchouli (Pogostemon cablin), cardamom (Elettariacardamomum) vetiver (Vetivertia zizanioides), orange (Citru sinensis L.osbeck), sandalwood (Santalum album), clary sage (Salvia sciarea), rose(Rosa centifolia), jasmine, (Jasminum grandiflorum), yarrow (Achilleamillefolium), tanacetum (Tanacetum annuum), ylang ylang (Canangaodorata) vetiver (Vetivertia zizanioides), rosemary (Rosmarinusofficinalis), birch (Betulalenta), grapefruit (Citrus paradisi), cypress(Cupressus sempervirens), peppermint (Mentha piperita), bay laurel(Laurus nobilis), black pepper (Piper nigrum), ginger root (Zingiberofficinale), juniper berry (Juniperus communis), lemongrass (Cymbopogonflexuosus) and wintergreen (Gaultheria procumbens).

The massage oil formulations of the present invention may also containtherapeutic agents, e.g., anti-infective agents, steroidal andnon-steroidal anti-inflammatory agents, in order to obtain a therapeuticeffect with the massage.

Lubricating Oils

The compositions of the present invention may also be utilize as alubricating formula in such cases which require lubrication of a skinarea The lubricating oils may also contain therapeutic agents, e.g.,anti-infective agents, steroidal and non-steroidal anti-inflammatoryagents, in order to obtain a therapeutic effect upon application.

Administration Via Dermal Patch

The compositions of the present invention may also be delivered to theskin using conventional dermal-type patches or articles, wherein theactive ingredients composition is contained within a laminatedstructure, that serves as a drug delivery device to be affixed to theskin. In such a structure, the active ingredients composition iscontained in a layer, or “reservoir”, underlying an upper backing layer.The laminated structure may contain a single reservoir, or it maycontain multiple reservoirs. In one embodiment, the reservoir comprisesa polymeric matrix of a pharmaceutically acceptable contact adhesivematerial that serves to affix the system to the skin during activeingredients delivery. Examples of suitable skin contact adhesivematerials include, but are not limited to, polyethylenes, polysiloxanes,polyisobutylenes, polyacrylates, polyurethanes, and the like. Theparticular polymeric adhesive selected will depend on the particularactive ingredients, vehicle, etc., i.e., the adhesive must be compatiblewith all components of the active ingredients-containing composition.Alternatively, the active ingredients-containing reservoir and skincontact adhesive are present as separate and distinct layers, with theadhesive underlying the reservoir which, in this case, may be either apolymeric matrix as described above, or it may be a liquid or hydrogelreservoir, or may take some other form.

The backing layer in these laminates, which serves as the upper surfaceof the device, functions as the primary structural element of thelaminated structure and provides the device with much of itsflexibility. The material selected for the backing material should beselected so that it is substantially impermeable to the activeingredients and to any other components of the active ingredientscontaining composition, thus preventing loss of any components throughthe upper surface of the device. The backing layer may be eitherocclusive or nonocclusive, depending on whether it is desired that theskin become hydrated during active ingredients delivery. The backing ispreferably made of a sheet or film of a preferably flexible elastomericmaterial. Examples of polymers that are suitable for the backing layerinclude polyethylene, polypropylene, and polyesters.

During storage and prior to use, the laminated structure includes arelease liner. Immediately prior to use, this layer is removed from thedevice to expose the basal surface thereof, either the activeingredients reservoir or a separate contact adhesive layer, so that thesystem may be affixed to the skin. The release liner should be made froman active ingredients/vehicle impermeable material.

Such devices may be fabricated using conventional techniques, known inthe art, for example by casting a fluid admixture of adhesive, activeingredients and vehicle onto the backing layer, followed by laminationof the release liner. Similarly, the adhesive mixture may be cast ontothe release liner, followed by lamination of the backing layer.Alternatively, the active ingredients reservoir may be prepared in theabsence of active ingredients or excipient, and then loaded by “soaking”in a active ingredients/vehicle mixture.

Therapeutic Effect and Dosage

The therapeutic efficacy of the compositions described herein can bedetermined by standard pharmaceutical procedures in experimental animalmodels or human beings. The data obtained from these studies can be usedin formulating a range of dosage for use in human (See e.g., Fingl, etal., 1975, in “The Pharmacological Basis of Therapeutics”, Ch1 p.1).

The effective concentration of the drug is calculated by proceduresknown in the art that can be employed to determine the effective localconcentration. For example, corticosteroid induced vasoconstriction inman may provide a preliminary useful hint to topical antiinflammatoryactivity.

The amount of a composition to be administered will, of course, bedependent on the subject being treated, the severity of the affliction,the manner of administration, the judgment of the prescribing physician,etc.

Short term studies over one or two weeks may not be the only relevantinvestigation for the clinical comparison of the topical drugs. Inpractice these are sometimes applied over long periods of time and thedifferences may be apparent only after months of treatment For thisreason, depending on the novelty of the product and the indicationsclaimed, certain studies of efficacy as well as of safety will berequired.

Since the hydrophobic agent can be derived from a biological source, itis necessary to assess the repeatability of the therapeutic effect aswell as the reproducibility, the specificity and the accuracy of theagent. This should be done by an analytical chemistry laboratory whichis defined as GLP (Good Laboratory Practice).

Compositions of the present invention may, if desired, be presented in abottle or jar or other container approved by the FDA, which may containone or more unit dosage forms containing the active ingredient.Compositions such as those described in the present invention may beparticularly susceptible to microbial and other contamination, andspecial measures need to be taken to prevent any contamination. The packor dispenser may also be accompanied by a notice associated with thecontainer in a form prescribed by a governmental agency regulating themanufacture, use or sale of pharmaceuticals, which notice is reflectiveof approval by the agency of the form of the compositions or human orveterinary administration. Such notice, for example, may be of labelingapproved by the U.S. Food and Drug Administration for prescription drugsor of an approved product insert compositions comprising a preparationof the invention formulated in a compatible pharmaceutical carrier mayalso be prepared, placed in an appropriate container, and labeled fortreatment of an indicated condition. Suitable conditions indicated onthe label may include treatment for acne or for psoriasis and the like.

The Gist and Advantages of the Present Invention Over the Prior Art.

The gist of the present invention is based on the striking discoverythat the addition of fatty alcohols to hydrophobic liquids, such assaturated, mono-unsaturated or poly-unsaturated oils, as well as mineraland silicone oils, may alter the physicochemical properties of thematerial, including the solidification thereof. This appears to beparticularly relevant when the fatty alcohol has a molecular weightgreater than 200 Da and at least one hydroxyl group in its chemicalstructure. The addition of a fatty alcohol to a liquid oil also givesrise to thixotropic properties (e.g., being semi-solid at rest andliquid upon application of shear forces thereto). This property enablesapplication of a thixotropic mixture as a semi-solid state to a bodysurface, which subsequently becomes substantially liquid and thereforemore spreadable and penetrable when rubbed onto the body surface. Thus,one of the most important properties of the carrier and composition ofthe present invention is that they are semi-solid at rest and that theyliquefy upon application of shear forces thereto. Semi-solid hydrophobicformulations are important not only for the pharmaceutical market butalso for cosmetic products, such as carriers of sunscreen compounds,oil-soluble plant extracts, materials for scrubbing purposes and otheractive and non-active cosmetic ingredients. Unlike aqueous liquids,which are rather easy to solidity due to their hydrogen bond formingability, oils are difficult to solidify. Several methods have beenproposed to increase the viscosity of oils. Various gelling agent, suchas inorganic complexing agents (U.S. Pat No. 4,780,309), hydrocolloids(U.S. Pat No. 4,576,645), polymers and copolymers (U.S. Pat No.5,985,821; 5,925,707), polysaccharides (U.S. Pat. No. 5,961,998) havebeen previously described in the context of solidifying oils for use infood and cosmetics. The use of waxes, fatty alcohols, fatty acids and 12hydroxy stearic acid in solidifying waste oils, in order to facilitatethe removal of such oils have also been described (JP-A-112385/1979;JP-A-106298/1980). U.S. Pat. No. 5,817,322 teaches pharmaceuticalcompositions, comprising an oil and beeswax as a gelling agent, whichform a netted framework of the beeswax and form a film after applicationon a body surface.

However, the prior art fails to teach a carrier or composition fortopical application which is semi-solid at rest and which liquefies uponapplication of shear forces thereto.

EXAMPLES

Additional objects, advantages, and novel features of the presentinvention will become apparent to one ordinarily skilled in the art uponexamination of the following examples, which are not intended to belimiting. Additionally, the various embodiments and aspects of thepresent invention as delineated hereinabove and as claimed in the claimssection below finds experimental support in the following examples.

Example 1 Preparation of a Corticosteroid Composition

Stearyl alcohol (60 grams) was heated to 80° C. USP olive oil (940grams) was heated to the same temperature. While at 80° C., the stearylalcohol was added to the preheated olive oil. 20 grams glycerin, 20grams tri-stearin, 1 gram of an antioxidant mixture were added byagitation. 1 gram of betamethasone valerate was added and the mixturewas poured into containers (25 gram tubes) and was allowed to coolspontaneously. While the mixture cooled to ambient temperature itgradually turned into a semi-solid.

Example 2 Efficacy of the Corticosteroid Composition for the Treatmentof Psoriasis

In a preliminary experiment, five patients with psoriasis were treatedwith the corticosteroid preparation described in Example 1, twice a day,for 10 days. In three out of five patients the psoriatic plaques andskin thickness were significantly reduced after 7-10 days of treatment(FIG. 1). The forth patient had a moderate improvement and fifth showedonly mild response to the treatment.

Example 3 A Double Blind Comparative Study Between the CorticosteroidComposition and a Conventional Ointment

Eight subjects were requested to apply 1 gram of the corticosteroidcomposition described in Example 1 on one arm and 1 gram of commercialbetamethasone valerate ointment, on the other arm. The study wasperformed in a double blind manner. The subjects had to describe theiropinion about the ease of application, ease of spreading, spreadabilityand penetrability of each of the products and to give their scores on ascale of 0 to 3 (0=poor, 1=barely acceptable; 2=acceptable and3=excellent).

As can be clearly seen in Table 3 below, the corticosteroid compositionof Example 1 obtained higher score in each of the study parameters.

TABLE 3 Comparison between the corticosteroid composition andBetamethasone commercial ointment Corticosteroid Commercial CompositionBetamethasone (Example 1) valerate ointment Parameters mean Score meanScore Ease of application 2.5 1.8 Ease of spreading 2.4 1.8Spreadability 2.8 1.6 Penetrability 2.4 2.0 Lack of stickiness 2.6 1.0Lack of greasiness 2.6 0.8 Lack of shiny look 1.9 1.4 Overall rating 2.61.6

Example 4 Ophthalmic Tetracycline Ointment

Behenyl alcohol (10 grams) was heated to 80° C. Light paraffin oil (90grams) was heated to the same temperature. While at 80° C., the behenylalcohol was added to the preheated oil. One gram of tetracycline wasadded and the mixture was poured into containers (5 gram tubes) and wasallowed to cool spontaneously. While the mixture cooled to ambienttemperature it gradually acquired a semi-solid state.

Example 5 Antiviral Ointment

Behenyl alcohol (10 grams) was heated to 80° C. Light paraffin oil (90grams) was heated to the same temperature. While at 80° C., the behenylalcohol was added to the preheated oil. One gram of reciclovir was addedand the mixture was poured into containers (5 gram tubes) and wasallowed to cool spontaneously. While the mixture cooled to ambienttemperature it gradually turned into a semi-solid.

Example 6 Antifungal Ointment

Behenic acid (10 grams) was heated to 80° C. Light paraffin oil (90grams) was heated to the same temperature. While at 80° C., the behenicacid was added to the preheated oil. Ten grams glycerin, 10 gramstri-stearin and 1 gram of an antioxidant mixture were added byagitation. 1.2 gram of bifinazole and 0.12 gram diflucortolone valeratewere added and the mixture was poured into containers (5 gram tubes) andwas allowed to cool spontaneously. While the mixture cooled to ambienttemperature it gradually turned into a semi-solid.

Example 7 Antibacterial Ointment

12-hydroxy stearic acid (10 grams) was heated to 80° C. Light paraffinoil (90 grams) was heated to the same temperature. While at 80° C., the12-hydroxy stearic acid was added to the preheated oil. Ten gramsglycerin, 10 grams tri-stearin and 1 gram of an antioxidant mixture wereadded by agitation. 2.4 grams of mupirocin were added and the mixturewas poured into containers (10 gram tubes) and was allowed to coolspontaneously. While the mixture cooled to ambient temperature itgradually turned into a semi-solid.

Example 8 Indulgence Massage Oil

Behenyl alcohol (6 grams) was heated to 80° C. A massage oil base,comprising sunflower oil, canola oil, sweet almond oil, sesame oil,macadamia nut oil, and tocopherol (92 grams) was heated to the sametemperature. While at 80° C., the behenyl alcohol was added to thepreheated oil. Four grams of a premix of essential oils of mandarinrange, sage, geranium rose, palmarosa, nutmeg, rosewood, cedarwood,patchouli, cardamom and vetiver was added and the mixture was pouredinto 100 ml bottles and was allowed to cool spontaneously. While themixture cooled to ambient temperature it gradually turned into asemi-solid.

Although the invention has been described in conjunction with specificembodiments thereof it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embraall such alternatives, modificationsand variations that fall within the spirit and broad scope of theappended claims. All publications, patents and patent applicationsmentioned in this specification are herein incorporated in theirentirety by reference into the specification, to the same extent as ifeach individual publication, patent or patent application wasspecifically and individually indicated to be incorporated herein byreference. In addition, citation or identification of any reference inthis application shall not be construed as an admission that suchreference is available as prior art to the present invention.

1. A pharmaceutical or cosmetic carrier, consisting essentially of: lessthan or equal to about 10 percent by weight of a solidifying agent, saidsolidifying agent consisting essentially of a long chain fatty alcoholhaving at least 15 carbon atoms in its carbon backbone and a fatty acidhaving at least 18 carbon atoms in its carbon backbone; and 75-99percent by weight of a hydrophobic solvent, wherein the carrier issemi-solid at rest and liquefies upon its application of shear forcesthereto.
 2. The pharmaceutical or cosmetic carrier of claim 1, whereinthe solidifying agent is present in an amount from about 6 percent byweight or less.
 3. The pharmaceutical or cosmetic carrier of claim 1,wherein the solidifying agent comprises fatty alcohols having at least20 carbons in the carbon chain.
 4. The pharmaceutical or cosmeticcarrier of claim 1, wherein the solidifying agent comprises fatty acidshaving at least 20 carbons in the carbon chain.
 5. The pharmaceutical orcosmetic carrier of claim 1, wherein the solidifying agent has at leastone alkyl group side chain in its carbon backbone.
 6. The pharmaceuticalor cosmetic carrier or composition of claim 1, wherein the carbonbackbone of the fatty acid or the fatty alcohol has at least onehydroxyl group on its carbon backbone.
 7. The pharmaceutical or cosmeticcarrier of claim 1, wherein the carbon backbone of said fatty acid orsaid fatty alcohol has at least one hydroxyl group at positions 8-14. 8.The pharmaceutical or cosmetic carrier of claim 1, wherein the fattyacid comprises a 12-hydroxy fatty acid.
 9. The composition of claim 1,wherein the hydrophobic carrier is selected from the group consisting ofmarine animal derived oils, terrestrial animal derived oils, mineraloils, silicone oils and plant derived oils.
 10. The composition of claim1, wherein the hydrophobic solvent comprises an oil selected from thegroup consisting olive oil, soybean oil, canola oil, rapeseed oil,cottonseed oil, coconut oil, palm oil, sesame oil, sunflower oil,safflower oil, rice bran oil, borage seed oil, syzigium aromaticum oil,hempseed oil, herring oil, cod-liver oil, salmon oil, corn oil, flaxseedoil, wheat germ oil, rape seed oil, evening primrose oil, rosehip oil,tea tree oil, melaleuca oil and jojova oil.
 11. The pharmaceutical orcosmetic carrier of claim 1, wherein the hydrophobic solvent includes anoil selected from the group consisting of omega-3 oil and omega-6 oil.12. The pharmaceutical or cosmetic carrier of claim 1, wherein at leastone of the solidifying agent and the hydrophobic solvent has atherapeutic or cosmetic beneficial effect.
 13. The pharmaceutical orcosmetic carrier of claim 1, wherein the carrier is formulated as amassage oil.
 14. The pharmaceutical or cosmetic carrier of claim 1,wherein the carrier is formulated as a lubricating oil.
 15. A method ofpreparing a pharmaceutical or cosmetic carrier, the method comprisingthe steps of: (a) mixing a hydrophobic solvent and a solidifying agentat a temperature above a melting temperature of the solidifying agent soas to obtain a mixture containing 75-99 percent by weight of thehydrophobic solvent and less than or equal to about 10 percent by weightof a solidifying agent, said solidifying agent consisting essentially ofa long chain fatty alcohol having at least 15 carbon atoms in its carbonbackbone and a fatty acid having at least 18 carbon atoms in its carbonbackbone; and (b) cooling the mixture.
 16. The method of claim 15,wherein the solidifying agent is present in an amount from about 6percent by weight or less.
 17. The method of claim 15, wherein thesolidifying agent comprises fatty alcohols having at least 20 carbons inthe carbon chain.
 18. The method of claim 15, wherein the solidifyingagent comprises fatty acids having at least 20 carbons in the carbonchain.
 19. The method of claim 15, wherein the solidifying agent has atleast one alkyl group side chain in its carbon backbone.
 20. The methodof claim 15, wherein the carbon backbone of the fatty acid or the fattyalcohol has at least one hydroxyl group on its carbon backbone.
 21. Themethod of claim 15, wherein the carbon backbone of said fatty acid orsaid fatty alcohol has at least one hydroxyl group at positions 8-14.22. The method of claim 15, wherein the fatty acid comprises a12-hydroxy fatty acid.
 23. The method of claim 15, wherein thehydrophobic carrier is selected from the group consisting of marineanimal derived oils, terrestrial animal derived oils, mineral oils,silicone oils and plant derived oils.
 24. The method of claim 15,wherein the hydrophobic solvent comprises an oil selected from the groupconsisting olive oil, soybean oil, canola oil, rapeseed oil, cottonseedoil, coconut oil, palm oil, sesame oil, sunflower oil, safflower oil,rice bran oil, borage seed oil, syzigium aromaticum oil, hempseed oil,herring oil, cod-liver oil, salmon oil, corn oil, flaxseed oil, wheatgerm oil, rape seed oil, evening primrose oil, rosehip oil, tea treeoil, melaleuca oil and jojova oil.
 25. The method of claim 15, whereinthe hydrophobic solvent includes an oil selected from the groupconsisting of omega-3 oil and omega-6 oil.
 26. The method of claim 15,wherein at least one of the solidifying agent and the hydrophobicsolvent has a therapeutic or cosmetic beneficial effect.
 27. Apharmaceutical or cosmetic composition consisting essentially of: (a) apharmaceutical or cosmetic carrier containing less than or equal toabout 10 percent by weight of a solidifying agent, said solidifyingagent consisting essentially of a long chain fatty alcohol having atleast 15 carbon atoms in its carbon backbone and a fatty acid having atleast 18 carbon atoms in its carbon backbone, and 75-99 percent byweight of a hydrophobic solvent; and (b) a therapeutically orcosmetically effective amount of a biologically active substance. 28.The pharmaceutical or cosmetic composition of claim 27, wherein thesolidifying agent is present in an amount from about 6 percent by weightor less.
 29. The pharmaceutical or cosmetic composition of claim 27,wherein the solidifying agent comprises fatty alcohols having at least20 carbons in the carbon chain.
 30. The pharmaceutical or cosmeticcomposition of claim 27, wherein the solidifying agent comprises fattyacids having at least 20 carbons in the carbon chain.
 31. Thepharmaceutical or cosmetic composition of claim 27, wherein thesolidifying agent has at least one alkyl group side chain in its carbonbackbone.
 32. The pharmaceutical or cosmetic composition of claim 27,wherein the carbon backbone of the fatty acid or the fatty alcohol hasat least one hydroxyl group on its carbon backbone.
 33. Thepharmaceutical or cosmetic composition of claim 27, wherein the carbonbackbone of said fatty acid or said fatty alcohol has at least onehydroxyl group at positions 8-14.
 34. The pharmaceutical or cosmeticcomposition of claim 27, wherein the hydrophobic carrier is selectedfrom the group consisting of marine animal derived oils, terrestrialanimal derived oils, mineral oils, silicone oils and plant derived oils.35. The pharmaceutical or cosmetic composition of claim 27, wherein thehydrophobic solvent comprises an oil selected from the group consistingolive oil, soybean oil, canola oil, rapeseed oil, cottonseed oil,coconut oil, palm oil, sesame oil, sunflower oil, safflower oil, ricebran oil, borage seed oil, syzigium aromaticum oil, hempseed oil,herring oil, cod-liver oil, salmon oil, corn oil, flaxseed oil, wheatgerm oil, rape seed oil, evening primrose oil, rosehip oil, tea treeoil, melaleuca oil and jojova oil.
 36. The pharmaceutical or cosmeticcomposition of claim 27, wherein the hydrophobic solvent includes an oilselected from the group consisting of omega-3 oil and omega-6 oil. 37.The pharmaceutical or cosmetic composition of claim 27, wherein at leastone of the solidifying agent and the hydrophobic solvent has atherapeutic or cosmetic beneficial effect.
 38. The pharmaceutical orcosmetic composition of claim 27, wherein the biologically active agentcomprises at least one of the solidifying agent or the hydrophobicsolvent.
 39. The pharmaceutical or cosmetic composition of claim 27,wherein said biologically active substance is selected from the group ofconsisting of an antibiotic agent, a free radical generating agent, anantifungal agent, an antiviral agent, a non-nucleoside reversetranscriptase inhibitor, a nucleoside-analog reverse transcriptaseinhibitor, a protease inhibitor, a non-steroidal antiinflammatory drug,an immunosuppressant, an antihistamine agent, an antiinflammatory agent,a retinoid agent, a tar agent, an antipruritics agent and a scabicideagent.
 40. The pharmaceutical or cosmetic composition of claim 27,wherein said biologically active substance is effective in the treatmentof a disease or disorder selected from the group consisting ofpsoriasis, acne, seborrhea, seborrheic dermatitis, alopecia andexcessive hair growth, ichthyosis, wounds, burns, cuts, ulcers,psoriasis, seborrheic dermatitis of the face and trunk, seborrheicblepharitis, contact dermatitis, stasis dermatitis and exfoliativedermatitis.
 41. A method of preparing a pharmaceutical or cosmeticcomposition, the method comprising the steps of (a) mixing a hydrophobicsolvent and a solidifying agent at a temperature above a meltingtemperature of the solidifying agent so as to obtain a pharmaceutical orcosmetic mixture containing 75-99 percent by weight of the hydrophobicsolvent and less than or equal to about 10 percent by weight of thesolidifying agent, said solidifying agent consisting essentially of along chain fatty alcohol having at least 15 carbon atoms in its carbonbackbone and a fatty acid having at least 18 carbon atoms in its carbonbackbone; and (b) further mixing into said carrier mixture atherapeutically or cosmetically effective amount of a biologicallyactive substance.
 42. The method of claim 41, wherein prior to said stepof mixing, both said hydrophobic solvent and said solidifying agent arebrought to said temperature above said melting temperature of saidsolidifying agent.